Abstract
Construction of spirocyclic pyrrolidines bearing a spiro quaternary stereocenter is an enormous challenge in synthetic organic chemistry. In this report, we introduce a Ag(I)/CAAA-amidphos-catalyzed enantioselective 1,3-dipolar cycloaddition between azomethine ylides and α-methylene-γ-butyrolactone as an effective strategy for the construction of excellent endo-selective spiro-[butyrolactone-pyrrolidine] derivatives. Meanwhile, the catalytic system was also successfully applied in the three-component one-pot reaction of azomethine ylides formed in situ under the action of N,N′-diisopropylcarbodiimide serving as a dehydrator. Under the optimal conditions, endo-pyrrolidine derivatives bearing a spiro quaternary stereocenter were obtained with high to excellent yields (up to 95% yield) and enantioselectivities (up to 93% ee).
Highlights
Substituted pyrrolidine motifs widely exist in natural alkaloids and bioactive molecules [1,2]
Various synthetic methods have been utilized for the chiral synthesis of spirocyclic pyrrolidine skeletons in recent years
Since the first asymmetric version of synthesis of spirooxindole-pyrrolidine derivatives was realized by Gong et al, via chiral BINOL-derived phosphoric acids, to catalyze the
Summary
Substituted pyrrolidine motifs widely exist in natural alkaloids and bioactive molecules [1,2]. Catalysts 2020, 10, 28 a key electron-deficient alkene in the asymmetric 1,3-dipolar cycloaddition to construct the highly substituted spirocyclic [butyrolactone-pyrrolidine] skeletons with multiple contiguous stereocenters, Catalysts 2019, 9, x FOR PEER REVIEW such skeletons with the lactone moiety have important biological activities. Via ofCu(I)/DTBM-BIPHEP-catalyzed α-methylene-γ-butyrolactonenecessary to realize the preparation such medicinally useful and synthetically challenging molecules involved process so far [24].selectivities. We firstly described the Ag(I)/CAAA-amidphos-catalyzed 1,3-dipolar cycloaddition between cycloaddition between α-imino esters and α-methylene-γ-butyrolactone as well as three-component α-imino esters and α-methylene-γ-butyrolactone as well as three-component one-pot reaction of αone-pot of α-imino esters formed inendo-selective situ, affording excellent endo-selective spirocyclic imino reaction esters formed in situ, affording excellent spirocyclic with high levels of enantioselectivities
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